SBRT With Cetuximab +/- Docetaxel Followed by Adjuvant Cetuximab +/- Docetaxel in Recurrent, Previously-Irradiated SCCHN

Randomized Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) With Cetuximab +/- Docetaxel Followed by Adjuvant Cetuximab +/- Docetaxel in Recurrent, Previously-Irradiated Squamous Cell Carcinoma of the Head and Neck (SCCHN)

The aim of this trial is to examine the addition of docetaxel on disease progression, metastasis and survival of patients otherwise treated with SBRT and cetuximab alone. To better resolve the impact of the experimental treatment the presence/absence of prior cetuximab treatment will be determine before assigning treatment to either cetuximab and SBRT only or cetuximab, SBRT, and docetaxel.

Study Overview

• Status: Completed
• Conditions: Squamous Cell Carcinoma of the Head and Neck Cancer; Previously-Irradiated
• Intervention / Treatment: Radiation: SBRT; Drug: Cetuximab; Drug: Docetaxel

Detailed Description

The aim of this trial is to examine the addition of docetaxel on the overall survival of patients otherwise treated with SBRT and cetuximab alone. In addition, we will determine the difference in progression free survival (PFS), the rate of local recurrence (LR) and of distant metastases (DM) across the SBRT and cetuximab + docetaxel arm and the arm receiving SBRT and cetuximab alone. To better resolve the impact of the experimental treatment on PFS, LR, and DM, patients will be stratified by the presence/absence of prior cetuximab treatment and then randomized to either the control arm (cetuximab and SBRT only) or the experimental arm (cetuximab, SBRT, and docetaxel).

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center - Radiation Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically-proven recurrent squamous cell carcinoma of the head and neck (SCCHN), who has received prior radiotherapy with or without chemotherapy. New primary is allowed if location is in a previously irradiated field. Biopsy is recommended for each recurrence but is not mandated per study. This will be at the discretion of the principal investigator.
• Prior radiation dose of at least 50 Gy.
• Disease confined to locoregional site and can be encompassed in a stereotactic body radiosurgery "portal"
• Tumor must be deemed to be inoperable or unresectable either by clinical or radiographic criteria. These criteria include encasement of great vessels, vertebral invasion or undue peri-operative risk.
• Prior surgery for recurrent or new SCCHN is allowed in previously irradiated patients. A minimum of 4 weeks should elapse between any surgery and treatment on study. However, high-risk pathologic features should be present, such as positive margins, positive lymphadenopathy, perineural or angiolymphatic invasion.
• Karnofsky performance status > 60 (ECOG 0-1)
• Prior treatment with an EGFR Inhibitor is allowed if it was a part of prior curative therapy and was completed at least 30 days prior to commencement of study therapy
• Any number of prior chemotherapy regimens are allowed
• Measurable disease on imaging studies (MRI, CT, PET-CT or physical exam)
• Age > 18
• Estimated life expectancy > 12 weeks
• No prior radiation therapy or chemotherapy within 1 month of study enrollment
• ANC > 1000, PLT>75,000, Serum creatinine<2.5 mg/dL, Bilirubin <1.5 x upper limits of normal (ULN)
• Diabetes must be controlled prior to PET-CT scanning (blood glucose <200 mg/dL)
• Ability to provide written informed consent

Exclusion Criteria:

• Evidence of distant metastasis on upright chest x-ray (CXR), computed tomography (CT) or other staging studies
• Patients in their reproductive age group should use an effective method of birth control. Patients who are breast-feeding, or have a positive pregnancy test will be excluded from the study
• Any co-morbidity or condition of sufficient severity to limit full compliance with the protocol per assessment by the investigator
• Concurrent serious infection
• History of known hypersensitivity to cetuximab, docetaxel or similar agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: SBRT + Cetuximab + Docetaxel followed by Cetuximab + Docetaxel; Previously Treated With Cetuximab - Group A; No Previous Cetuximab - Group C	Radiation: SBRT; 8.8-10 Gy per fraction (total: 44-50 Gy); Other Names: CyberKnife; Trilogy; True Beam; Radiosurgery; Stereotactic radiosurgery; Drug: Cetuximab; Day -7 (One week prior to commencement of stereotactic radiosurgery): Cetuximab, 400 mg/m2 Days 0 and 8 (The 1st and 2nd week of radiosurgery): Cetuximab, 250 mg/m2 Cetuximab, 250 mg/m2 will be given weekly ( following radiosurgery); Other Names: Erbitux; Drug: Docetaxel; Days 0 and 8 (The 1st and 2nd week of radiosurgery) Docetaxel, 25 mg/m2 Docetaxel, 25 mg/m2 will be given weekly (following radiosurgery); Other Names: Taxotere
Other: SBRT + Cetuximab followed by Cetuximab; Previously Treated with Cetuximab - Group B; No Previous Cetuximab - Group D	Radiation: SBRT; 8.8-10 Gy per fraction (total: 44-50 Gy); Other Names: CyberKnife; Trilogy; True Beam; Radiosurgery; Stereotactic radiosurgery; Drug: Cetuximab; Day -7 (One week prior to commencement of stereotactic radiosurgery): Cetuximab, 400 mg/m2 Days 0 and 8 (The 1st and 2nd week of radiosurgery): Cetuximab, 250 mg/m2 Cetuximab, 250 mg/m2 will be given weekly ( following radiosurgery); Other Names: Erbitux

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-Year Locoregional Progression-free survival (PFS)	The proportion of previously-irradiated patients treated with SBRT, cetuximab, and/or docetaxel, evaluated by PET/CT per RECIST Criteria v1.1 that do not experience locoregional disease progression within one year. Per RECIST, Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s).	Up to 12 months
Incidence of distant disease	The proportion of patients with distant disease evaluated by PET/CT or CT per RECIST Criteria v1.1. Malignant disease that has spread to other organs or to lymph nodes other than those near the primary tumor. Per RECIST, Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s).	Up to 12 months
Acute toxicities	Adverse Events and Serious Adverse Events determined by patient follow up per CTCAE v4.0 criteria.	Up to 3 months after SBRT treatment
Late toxicities	Adverse Events and Serious Adverse Events determined by patient follow up per CTCAE v4.0 criteria.	From 3 months after SBRT treatment, up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Incidence of either a confirmed Complete Response (CR) or Partial Response (PR), per RECIST Criteria v1.1. Per RECIST, CR is defined as the disappearance of all target lesions. To be assigned a status of complete response, changes in tumor measurements must be confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met. PR is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter. To be assigned a status of partial response, changes in tumor measurements must be confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met.	Up to 12 months
Overall Survival (OS)	Time from the date of randomization to the date of death due to any cause.	Up to 5 years
University of Washington QOL Assessment Tool (UW-QOL)	The UW-QOL is a patient-reported outcome measure consisting of domains based upon discrete ordinal responses regarding their past 7 days. Scoring is scaled to so that a score of 0 represents the worst possible response, and a score of 100 represents the best possible response. 12 single question domains, these having between 3 and 6 response options that are scaled evenly from 0 (worst) to 100 (best) according to the hierarchy of response. The domains are pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder, taste, saliva, mood and anxiety. Another question asks patients to choose up to three of these domains that have been the most important to them. There are also three global questions, one about how patients feel relative to before they developed their cancer, one about their health-related QOL and one about their overall QOL.	Up to 5 years
Progression-free Survival (PFS)	Time from the date of entry on study to the date of progression per RECIST Criteria v1.1 or the date of death from any cause. Subjects who are alive and have not progressed will be censored at their last follow-up date. Per RECIST, Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s).	Up to 5 years

Collaborators and Investigators

• Sponsor: Heath Skinner
• Investigators: Principal Investigator: David A Clump, MD, UPMC Hillman Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2013
• Primary Completion (Actual): March 15, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: January 30, 2014
• First Submitted That Met QC Criteria: February 4, 2014
• First Posted (Estimated): February 6, 2014

Study Record Updates

• Last Update Posted (Actual): June 5, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Stereotactic Body Radiation Therapy (SBRT)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Cetuximab
• Other Study ID Numbers: HCC 11-112

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes